HOXD10 is a sequence-specific transcription factor that functions as a developmental regulator providing cells with positional identities along the anterior-posterior axis [UniProt]. It binds double-stranded DNA and regulates transcription through RNA polymerase II [GO Annotations]. Mechanistically, HOXD10 acts as a transcriptional repressor in multiple contexts. In renal fibrosis, HOXD10 directly binds to the NOX4 promoter and inhibits its transcription, thereby reducing ferroptosis-mediated oxidative stress and fibrosis progression 1. In cancer, HOXD10 is targeted by miR-10b, and its suppression promotes cancer cell migration and invasion in gastric and bladder cancers, with HOXD10 regulating downstream effectors like E-cadherin and MMP14 23. HOXD10 is also dysregulated in colorectal cancer stem cells, where altered transcriptional regulation of HOXD10 contributes to tumorigenesis 4. Disease relevance extends beyond cancer. HOXD10 is hypermethylated across all 16 major cancer types, suggesting epigenetic silencing as a cancer mechanism 5. A novel pathogenic variant (p.S80R) was identified in Müllerian duct anomalies, revealing HOXD10's role in reproductive development 6. CKD-related renal fibrosis also involves HOXD10 downregulation, with promoter hypermethylation observed 1. Clinically, HOXD10 represents a potential therapeutic target for kidney disease through AAV-mediated gene therapy and a candidate biomarker for cancer diagnosis and prognosis assessment.